Head and Neck Diseases by Alexandros G.Sfakianakis: 12/06/17

Τετάρτη 6 Δεκεμβρίου 2017

Long-term stability of dental adhesive incorporated by boron nitride nanotubes

Publication date: Available online 6 December 2017
Source:Dental Materials
Author(s): Felipe Weidenbach Degrazia, Vicente Castelo Branco Leitune, Fernanda Visioli, Susana Maria Werner Samuel, Fabrício Mezzomo Collares
ObjectiveThe aim of this study was to evaluate physicochemical properties, long-term microtensile bond strength and cytotoxicity of methacrylate-based adhesive containing boron nitride nanotubes (BNNTs) as fillers.MethodsA dental adhesive was formulated using BisGMA/HEMA, 66/33wt% (control). Inorganic BNNT fillers were incorporated into the adhesive at different concentrations (0.05, 0.075, 0.1 and 0.15wt%). Analyses of degree of conversion (DC), polymerization rate [Rp.(s⁻¹)], contact angle (CA) on dentin, after 24h and 6 months microtensile bond strength (μTBS-24h and 6 months) were assessed. Cytotoxicity was performed through viability of fibroblast cells (%) by sulforhodamine B (SRB) colorimetry.ResultsDC and max. polymerization rate increased (p<0.05) after incorporating 0.075 and 0.1wt% BNNT. The contact angle on dentin increased (p<0.05) after incorporating 0.15wt% BNNT. The μTBS-24h showed no changes (p>0.05) after incorporating up to 0.15wt% BNNT comparing to control. After 6 months, μTBS decreased (p<0.05) for control and 0.15wt% BNNT and BNNT groups up to 0.15wt% showed higher μTBS than control (p<0.05). No difference of fibroblast growth was found among adhesives (p>0.05) and up to 19% of cell viability was found comparing 0.05wt% BNNT to positive control group (100%).SignificanceIncorporating boron nitride nanotubes up to 0.1wt% into dental adhesive increased the long-term stability to dentin without decreasing viability of fibroblast cell growth. Thus, the use of BNNTs as filler may decrease failure rate of current dentinal adhesives.

http://ift.tt/2AfomAN

Varicella pseudo-Koebner phenomenon associated with vascular access opening

http://ift.tt/2AirVX2

Circadian and endocrine rhythms

Publication date: October 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 31, Issue 5
Author(s): Andries Kalsbeek, Eric Fliers

http://ift.tt/2j26amL

Varicella pseudo-Koebner phenomenon associated with vascular access opening

http://ift.tt/2AirVX2

Successful management of retinal metastasis from renal cancer with everolimus in a monophthalmic patient: a case report

The retina is an uncommon site for metastases, in particular from solid tumors. Some authors have reported a recent increase in the incidence of metastases in infrequent sites, such as brain or bone, probably ...

http://ift.tt/2Ah4GN1

Dislocation network in additive manufactured steel breaks strength–ductility trade-off

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Leifeng Liu, Qingqing Ding, Yuan Zhong, Ji Zou, Jing Wu, Yu-Lung Chiu, Jixue Li, Ze Zhang, Qian Yu, Zhijian Shen
Most mechanisms used for strengthening crystalline materials, e.g. introducing crystalline interfaces, lead to the reduction of ductility. An additive manufacturing process – selective laser melting breaks this trade-off by introducing dislocation network, which produces a stainless steel with both significantly enhanced strength and ductility. Systematic electron microscopy characterization reveals that the pre-existing dislocation network, which maintains its configuration during the entire plastic deformation, is an ideal "modulator" that is able to slow down but not entirely block the dislocation motion. It also promotes the formation of a high density of nano-twins during plastic deformation. This finding paves the way for developing high performance metals by tailoring the microstructure through additive manufacturing processes.

Graphical abstract

http://ift.tt/2AB0Aht

Improving solar cells with light and humidity

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson

http://ift.tt/2jlV7C3

Microbots that use magnetism to capture cells

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson

http://ift.tt/2ABbjZE

Polymer-coated gold nanocages control cells’ fate

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Cordelia Sealy

http://ift.tt/2jlV5tV

European team tunes LEDs

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley

http://ift.tt/2AA2r6f

Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Gopu Sriram, Massimo Alberti, Yuri Dancik, Bo Wu, Ruige Wu, Zhaoxu Feng, Srinivas Ramasamy, Paul Lorenz Bigliardi, Mei Bigliardi-Qi, Zhiping Wang
Reconstruction of full-thickness skin equivalents with physiologically relevant cellular and matrix architecture is gaining importance as an in vitro tool for basic research, and for the pharmaceutical, toxicological, and cosmetic industries. However, human skin equivalents reconstructed on traditional culture systems are limited by a weak skin barrier function compared to normal human skin. Probable reasons include the lack of mechanical forces and dynamic flow system that provide necessary mechanistic signals and continuous supply and/or drainage of nutrients and metabolites. Here, we combine a fibrin-based dermal matrix with a biomimetic 'organ-on-chip' system for the development of human skin equivalents that better recapitulate the structure and functionalities of human skin, compared to conventional static culture systems. We demonstrate that dynamic perfusion and a fine control of the microenvironment enable improved epidermal morphogenesis and differentiation, and enhanced barrier function. It is also shown that integrated 3D culturing and integrity/permeability testing can be conducted directly on the organ-on-chip device owing to the non-contracting properties of the fibrin-based dermal matrix, thus overcoming the limitations of collagen-based skin equivalents used in conventional cell culture inserts and diffusion cells. With this scalable system, it is possible to achieve higher throughput and automation of culture and testing protocols, and deliver low-cost alternatives to animal and clinical studies for drug screening and toxicological applications.

Graphical abstract

http://ift.tt/2jmoaVN

Automotive Weight Reduction Expo 2018

Publication date: Available online 6 December 2017
Source:Materials Today

http://ift.tt/2Ay5yvI

New diode displays purest green light

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson

http://ift.tt/2jot0Sw

Massless magnets

Publication date: Available online 6 December 2017
Source:Materials Today

http://ift.tt/2AzZKBK

Useful hybrid photoactive materials produced

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson

http://ift.tt/2jobJJ9

Nanomanufacturing made quicker

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson

http://ift.tt/2ABLg4a

Recent advances in emerging 2D nanomaterials for biosensing and bioimaging applications

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Wei Wen, Yang Song, Xu Yan, Chengzhou Zhu, Dan Du, Shengfu Wang, Abdullah M. Asiri, Yuehe Lin
The great success of graphene throws new light on discovering more two-dimensional (2D) layered nanomaterials that stem from atomically thin 2D sheets. Compared with a single element of graphene, emerging graphene-like 2D materials composed of multiple elements that possess more versatility, greater flexibility and better functionality with a wide range of potential applications. In this review, we provide insights into the rapidly emerging 2D materials and their biosensing and bioimaging applications in recent three years, including 2D transition metal nanomaterials, graphitic nitride materials, black phosphorus, and emerging 2D organic polymers. We first briefly highlight their unique 2D morphology and physicochemical properties and then focus on their recent applications in electrochemical biosensing, optical biosensing and bioimaging. The challenges and some thoughts on future perspectives in this field are also addressed.

Graphical abstract

http://ift.tt/2jnQNCi

ZnO tetrapod materials for functional applications

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Yogendra Kumar Mishra, Rainer Adelung
In the last 15 years, more than 50,000 papers with zinc oxide (ZnO) in the title are listed within ISI database. The outstanding popularity of ZnO has many reasons; the most important one appears to be its multi-functionality, resulting in applications in physics, chemistry, electrical engineering, material science, energy, textile, rubber, additive manufacturing, cosmetics, and pharmaceutical or medicine, as well as the ease to grow all kinds of nano- and microstructures. A key structure is the tetrapod-shaped ZnO (T-ZnO), which we want to focus on in this mini-review to demonstrate the remarkable properties and multifunctionality of ZnO and motivate why even much more research and applications are likely to come in near future. As T-ZnO came into focus again mainly during the last 10 years, the big data problem in T-ZnO is not as severe as in ZnO; nevertheless, a complete overview is impossible. However, this brief T-ZnO overview attempts to cover the scopes toward advanced technologies; nanoelectronics/optoelectronics sensing devices; multifunctional composites/coatings; novel biomedical engineering materials; versatile energy harvesting candidates; and unique structures for applications in chemistry, cosmetics, pharmaceuticals, food, agriculture, engineering technologies, and many others. The 3D nanotechnology is a current mainstream in materials science/nanotechnology research, and T-ZnO contributes to this field by its simple synthesis of porous networks as sacrificial templates for any desired new cellular materials.

Graphical abstract

http://ift.tt/2AxF4dH

Chameleon materials

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley

http://ift.tt/2jnKrmt

Bioactive origami with “tissue” paper

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley

http://ift.tt/2ABP0TD

Nanoparticles trick immune system into action

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Cordelia Sealy

http://ift.tt/2jo4KA5

Polymer composite combines novel properties

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Cordelia Sealy

http://ift.tt/2AyO2Yc

Tunable materials that can change between mirror and window

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson

http://ift.tt/2jogF0B

Is modern diesel cleaner than cold-start gasoline?

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley

http://ift.tt/2AAamAH

Dengue re-emergence in Delhi: Lessons to learn

Publication date: Available online 6 December 2017
Source:Medical Journal Armed Forces India
Author(s): Ram Kumar Mishra

http://ift.tt/2jlPgwq

Primary sinonasal tuberculosis: Our experiences in a tertiary care hospital of eastern India

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Santosh Kumar Swain, Ishwar Chandra Behera, Mahesh Chandra Sahu
BackgroundPrimary sinonasal tuberculosis is an extremely rare clinical entity. Often the clinician fail to diagnose the primary sinonasal tuberculosis, so treatment is frequently delayed and leading to complications.ObjectiveTo evaluate the clinical profile, diagnostic tools, treatment and outcome of primary sinonasal tuberculosis.Materials and MethodsRetrospective studies of six cases of primary sinonasal tuberculosis were done over period of five years. The detail clinical profile, diagnosis, treatment and outcome were studied in these patients.ResultsOut of the six cases of primary sinonasal tuberculosis, four cases were female and two were male. The mean age during the time of diagnosis was 35 years (16–67 years). The most common clinical presentations were chronic nasal obstruction, epistaxis and ulcerations at the nasal vestibule and nasal cavity. Diagnosis was confirmed by Histopathological diagnosis in all six cases. All cases received antitubercular therapy for 6–9 months. All six patients successfully responded to antitubercular therapy. Two year follow up showed no relapse, dissemination and death.ConclusionPrimary sinonasal tuberculosis is a rare clinical entity. It is always suspected among the patients with nasal obstruction, epistaxis and ulcerations at nasal vestibule and nasal cavity in the region with high prevalence of Tuberculosis.

http://ift.tt/2BGXUwi

The role of Mannose-binding lectin 2 (MBL2) gene polymorphisms in adenoid hypertrophy among young children

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Husam Majeed Hameed, Ali S. Dawood
ObjectiveIs to determine the role of Mannose binding lectin (MBL) 2 (SNP 49 C/T rs#5030737) gene polymorphism among patients with adenoidal hypertrophy in Iraqi population.MethodsFrom July through December 2015, a total of 60 adenoid hypertrophy (study group) young child patients (35 males and 25 females) with an age between (4 and 12) years old, were enrolled in this study according to selection criteria. A second group of otherwise healthy young child who did not have any symptoms or signs of adenoid hypertrophy were considered to be a control group. Confirmation of adenoid hypertrophy was achieved by: clinical examination, radiological assessment of postnasal space and an endoscopic nasopharyngoscopy. Blood samples were collected from both groups and genotyping of MBL-2 gene polymorphism was performed using traditional PCR and allele-specific technique.ResultsMBL2 gene polymorphism and allele frequencies among adenoid hypertrophy patients and their control were studied and the results showed that CC = 40 (66.7%), TT = 13(21.7%), and CT = 7 (11.6) in study group, while in control group CC = 5(8.3), TT = 9 (15%).CT = 46 (67.7%). The P-value of genotypes (CC, TT and CT) in study groups versus the control group were P < 0.001 (highly significant), P = 0.435 (non-significant) and P < 0.001 (highly significant) respectively.ConclusionThe difference between the MBL2 (SNP 49 C/T rs#5030737) gene polymorphism among adenoid hypertrophy patients and healthy people may indicate it could be used as an early predictive factor for children whom will be prone to adenoid hypertrophy. The genotype CC could be considered as a risk factor while CT genotype could be considered a protective factor against adenoid hypertrophy in the current study. A further study needed to evaluate the use of the above mentioned polymorphism as a prognostic value foradenoid hypertrophy.

http://ift.tt/2ivYOUJ

Surgical strategy for frontal sinus inverted papilloma

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): A.A. Ibrahim, Haitham Morsi, Mohamed Hassab, Mohamed Eid, Samy Elwany
Inverted papilloma (IP) is a benign tumor with a local aggressive nature and has a tendency to recur after excision. Despite the evolution of endoscopic techniques in the management of IP, external approaches still play a crucial role in frontal sinus involvement.ObjectiveThe present study aimed at planning a strategy for managing IP arising in or involving the frontal recess and/or frontal sinus.Patients and methodsTen patients with frontal sinus IP were enrolled in the present study. The type of surgical procedure was tailored according to the site of origin and extent of the tumor.ResultsFive combined surgeries and five extended endoscopic surgeries were performed in 1 year and 4 months with a follow up period of 2 years. Complete resection of the tumor was achieved in all the cases and no recurrences were reported at the end of the follow up period.ConclusionsThe exact approach to frontal sinus IP differ from one case to the other. Endoscopic frontal surgery is the mainstay in treatment of frontal sinus IP. External or combined approaches still remain a valid option for lesions affecting the mucosa of the frontal sinus extensively or extending far lateral.

http://ift.tt/2BFxLxG

Intracranial metastasis of follicular thyroid carcinoma mimicking cerebellopontine angle tumour

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Li Yun Lim, Jamuneswary Selvarajoo, Norhafiza Mat Lazim, Ing Ping Tang
Cerebellopontine angle (CPA) tumour is most commonly associated acoustic neuroma. The occurrence of metastatic brain tumour at CPA is rare. Follicular thyroid carcinoma is second most common well differentiated thyroid malignancy and brain metastasis is unusual. We would like to report an unusual presentation of follicular thyroid carcinoma with brain metastasis at the CPA region. A 60 year old gentleman presented with occipital headache, slurred speech with positive cerebellar signs and multiple cranial nerve palsies with no neurological deficit to upper and lower limbs. No other significant findings noted on examination. Imaging investigations revealed a CPA tumour. Transnasal transphenoidal tumour debulking was done and biopsy revealed a metastasis of follicular thyroid carcinoma. After total thyroidectomy, the patient was scheduled for radioactive iodine ablation. Metastasis brain tumour with high vascular supply can contribute to difficult tumour debulking. Embolisation and stereotactic therapy are the supporting and alternative method of treatment.

http://ift.tt/2iwP2Sr

Atypical multiple metastasis of recurrent pleomorphic adenoma

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Darshini Nagarajah, Irfan Mohamad, Norhafiza Mat Lazim, Sharifah Emilia Tuan Sharif, Nur Hidayati Mohamad Pakarul Razy
Pleomorphic adenoma is the commonest benign neoplasm of the parotid gland and minor salivary glands. It is composed of epithelial and myoepithelial cells arranged in various morphological patterns. The concrete reasons contributing to a recurrent disease are obvious or attempts of accidental tumor spillage, enucleation with rupture and incomplete excision during operation. The other solid reasons that could contribute to recurrence are known incomplete pseudocapsule, extracapsular extensions, pseudopods of pleomorphic adenoma tissue, and satellite pleomorphic beyond the pseudocapsule matrix. Most recurrent pleomorphic adenoma are multinodular with different recurrent sites and time duration. We describe a case of 55-year-old lady who underwent left superficial parotidectomy for pleomorphic adenoma 14 years prior to current presentation. After 8 years, she presented with ipsilateral level II lymph node, in which excision showed pleomorphic adenoma. Within 2 years after excision, she experienced another multiple small neck swellings at the level II-III, in which histopathology examination of the excised masses were consistent with pleomorphic adenoma, without evidence of lymph node background to suggest metastasis.

http://ift.tt/2BGKX5N

Do Resident Case Logs Meet ACGME Requirements? A Comparison Between Acute Care and Elective Cases

Publication date: Available online 6 December 2017
Source:Journal of Surgical Education
Author(s): Kathryn R. Wolf, Zachary A. Taylor, Sarah B. Placek, Michael W. Tsai, Brenton R. Franklin, E. Matthew Ritter
PurposeOperative experience is at the core of general surgery residency, and recently operative volume requirements for graduating residents were increased. The ACGME has outlined 4 areas of required resident participation and documentation in order for a surgical case to be logged: determination or confirmation of the diagnosis, provision of preoperative care, selection and accomplishment of the operative procedure, and direction of the postoperative care. The purpose of this study was to examine whether general surgery residents are currently meeting the required care participation documentation standard and to examine the effect of acute care vs. elective cases on documentation.MethodsThe operative case logs of 7 PGY-3 and 7 PGY-5 general surgery residents from March 2016 were retrospectively reviewed and compared to the electronic medical record (EMR) to verify documentation of resident participation in each of the 4 required areas. Chart review was also utilized to classify cases as either acute care or elective.ResultsA total of 339 cases were reviewed (159 PGY-3 and 180 PGY-5). Of these, 251 cases were classified as elective and 88 were classified as acute care. Overall, documentation of comprehensive care (participation in all four required areas) was found for 44% of cases, with residents reporting participation in a higher percentage of comprehensive care (all 4 domains completed) than was actually documented in the EMR (71.9% vs. 44.4%, t[13] = 2.57, p = 0.023, d = 1.13). Comprehensive care was documented more frequently in elective cases than acute care cases (49.7% vs. 38.3%), and there was less discrepancy between perceived and documented comprehensive care within elective cases (67% vs. 49.7%, t[13] = 1.17, p = 0.27) than acute care cases (80.9% vs. 38.3%, t[13] = 4.40, p = 0.001).ConclusionsDespite ACGME requirements, the majority of cases logged by general surgery residents do not have documentation by the operating resident in the EMR verifying provision of comprehensive care. Elective cases were more likely to meet documentation requirements than acute care cases, and we purport that this is possibly secondary to restricted work hours. We expect that other programs would find similar compliance in the documentation of comprehensive care. These results question whether the requirement for documenting comprehensive care to log a surgical case is practical in surgical residency training, particularly with an increasing demand for operative volume in the setting of limited work hours.

http://ift.tt/2BHdsQx

Primary sinonasal tuberculosis: Our experiences in a tertiary care hospital of eastern India

The role of Mannose-binding lectin 2 (MBL2) gene polymorphisms in adenoid hypertrophy among young children

Surgical strategy for frontal sinus inverted papilloma

Intracranial metastasis of follicular thyroid carcinoma mimicking cerebellopontine angle tumour

Atypical multiple metastasis of recurrent pleomorphic adenoma

Issue Information - TOC

No abstract is available for this article.

http://ift.tt/2zVymec

Issue Information - Journal Info page

No abstract is available for this article.

http://ift.tt/2nBVZXL

Wrist accelerometry for physical activity measurement in individuals with spinal cord injury – a need for individually calibrated cut-points

Publication date: Available online 6 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Laura A. McCracken, Jasmin K. Ma, Christine Voss, Franco H.N. Chan, Kathleen A. Martin Ginis, Christopher R. West
ObjectiveTo create and compare individual and group-based cut-points for wrist-accelerometry that corresponds to moderate-to-vigorous physical activity (MVPA) in people with spinal cord injury (SCI).DesignParticipants completed a graded treadmill-wheeling test while being assessed for oxygen consumption, wrist-acceleration vector magnitude, and spoke acceleration. Oxygen consumption was converted to SCI metabolic equivalents (SCI METS) and linear regression was applied to determine an individualized vector magnitude cut-point (counts per minute, VM-CPM) corresponding with MVPA (≥3 SCI METS). Multilevel linear regression was applied to determine a group MVPA cut-point. Participants then completed a 6-day monitoring period while wearing the accelerometers.SettingA local SCI research centre.ParticipantsTwenty manual wheelchair users (30-64yrs, C5-L1) with chronic (>1 year) SCI.InterventionsNot applicable.Main outcome measuresMean total daily MVPA, wheeled MVPA, and non-wheeled MVPA were calculated using both the individual and group cut-points. Agreement on measures of min/day of MVPA between the individual and group mean cut-point method was compared using Bland-Altman plots.ResultsIndividual cut-points for MVPA ranged from 6040 to 21540 VM-CPM, with a group cut-point of 11652 (CI 7395 – 15909). For total daily MVPA, Bland-Altman analysis revealed a bias of 0.22 ± 33.0 minutes, with 95% limits of agreement from -64.5 to 64.9 minutes, suggesting a large discrepancy between total MVPA calculated from individual and group-mean cut-points.ConclusionsIndividual calibration of wrist-worn accelerometry is recommended for effective habitual PA monitoring in this population.

http://ift.tt/2AD3VdU

Role of Dopamine Receptors in the Anticancer Activity of ONC201

Publication date: January 2018
Source:Neoplasia, Volume 20, Issue 1
Author(s): Christina Leah B. Kline, Marie B. Ralff, Amriti R. Lulla, Jessica M. Wagner, Phillip H. Abbosh, David T. Dicker, Joshua E. Allen, Wafik S. El-Deiry
ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in ONC201's anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type–specific manner. On the other hand, DRD3 was generally not detectable. Overexpressing DRD2 in cells with low DRD2 levels increased ONC201-induced PARP cleavage, which was preceded and correlated with an increase in ONC201-induced CHOP mRNA expression. On the other hand, knocking out DRD2 using CRISPR/Cas9 in three cancer cell lines was not sufficient to abrogate ONC201's anticancer effects. Although ONC201's anticancer activity was not dependent on DRD2 expression in the cancer cell types tested, we assessed the cytotoxic potential of DRD2 blockade. Transient DRD2 knockdown in HCT116 cells activated the integrated stress response and reduced cell number. Pharmacological antagonism of DRD2 significantly reduced cell viability. Thus, we demonstrate in this study that disrupting dopamine receptor expression and activity can have cytotoxic effects that may at least be in part due to the activation of the integrated stress response. On the other hand, ONC201's anticancer activity goes beyond its ability to antagonize DRD2, potentially due to ONC201's ability to activate other pathways that are independent of DRD2. Nevertheless, blocking the dopamine D1-like receptor DRD5 via siRNA or the use of a pharmacological antagonist promoted ONC201-induced anticancer activity.

http://ift.tt/2zXoGQI

Limitations in learning: How treatment verifications fail and what to do about it?

Publication date: Available online 6 December 2017
Source:Brachytherapy
Author(s): Susan Richardson, Bruce Thomadsen
PurposeThe purposes of this study were: to provide dialog on why classic incident learning systems have been insufficient for patient safety improvements, discuss failures in treatment verification, and to provide context to the reasons and lessons that can be learned from these failures.Methods and MaterialsHistorically, incident learning in brachytherapy is performed via database mining which might include reading of event reports and incidents followed by incorporating verification procedures to prevent similar incidents. A description of both classic event reporting databases and current incident learning and reporting systems is given. Real examples of treatment failures based on firsthand knowledge are presented to evaluate the effectiveness of verification. These failures will be described and analyzed by outlining potential pitfalls and problems based on firsthand knowledge.ResultsDatabases and incident learning systems can be limited in value and fail to provide enough detail for physicists seeking process improvement. Four examples of treatment verification failures experienced firsthand by experienced brachytherapy physicists are described. These include both underverification and oververification of various treatment processes.ConclusionsDatabase mining is an insufficient method to affect substantial improvements in the practice of brachytherapy. New incident learning systems are still immature and being tested. Instead, a new method of shared learning and implementation of changes must be created.

http://ift.tt/2nDdmam

Treatment planning considerations for permanent breast seed implant

Publication date: Available online 6 December 2017
Source:Brachytherapy
Author(s): Amy Frederick, Tyler Meyer, Michael Roumeliotis
PurposeTo determine an optimal planning strategy for permanent breast seed implant that minimizes dose heterogeneity without degrading coverage and conformity.Methods and MaterialsA simple model was developed to investigate planning strategies incorporating a range of ¹⁰³Pd seed activities, needle and seed spacings, and implants in which seed positions are either restricted to or permitted outside of spherical planning target volumes (PTVs). To address more realistic target geometries, model parameters were used to retrospectively replan a 10-patient cohort in MIM Symphony.ResultsWe confirm that the current clinical modified uniform implantation pattern provides the most favorable dose distributions, given the resolution of the template grid and spacer length. We show that needle and seed counts for replans with seed placement permitted 0.3 cm outside of the PTV are most comparable to clinical preplans, but offer a 13 ± 11% average reduction in the VPTV150%. Replans produced with seed placement 0.5 cm outside of the PTV provide the largest improvement in dose homogeneity, at the cost of a slight increase in irradiated volume and an increase in the number of needles and seeds.ConclusionsImplanting seeds beyond the PTV within a 0.3–0.5 cm margin, and optimizing seed activity on a per patient basis, allows for improvement in dose homogeneity. However, these plans require higher needle and seed counts and result in a small increase in irradiated volume. Before planning recommendations can be made, the implications of these changes must be investigated in the context of clinical outcome for permanent breast seed implant.

http://ift.tt/2zULIHU

Asymmetrical Arterial Diameters

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Wolfgang G. Mouton, André Wyss

http://ift.tt/2B8kZM2

Re: “Management of Atherosclerotic Carotid and Vertebral Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)”

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Karl Sörelius

http://ift.tt/2Aghmng

Floating Aortic Thrombus in a Non-aneurysmal and Non-atherosclerotic Aorta

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): C. Sosa, F. Zuccarino

http://ift.tt/2BaA5Rh

Response to “Re. Management of Atherosclerotic Carotid and Vertebral Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)”

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A Ross Naylor, Jean-Baptiste Ricco

http://ift.tt/2AhMhzs

Double Banana Technique: A Fruity Solution for Treating Iliac Aneurysms After Aortic Surgery

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Lucie Salomon du Mont, Simon Rinckenbach

http://ift.tt/2B8QZQq

Efficient Differentiation of Bone Marrow Mesenchymal Stem Cells into Endothelial Cells in Vitro

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Chengen Wang, Yuan Li, Min Yang, Yinghua Zou, Huihui Liu, Zeyin Liang, Yue Yin, Guochen Niu, Ziguang Yan, Bihui Zhang
ObjectiveEndothelial cells (ECs) play an important role in neovascularisation, but are too limited in number for adequate therapeutic applications. Mesenchymal stem cells (MSCs) have the potential to differentiate into endothelial lineage cells, which makes them attractive candidates for therapeutic angiogenesis. The aim of this study was to investigate efficient differentiation of MSCs into ECs by inducing medium in vitro.MethodsMSCs were isolated from bone marrow by density gradient centrifugation. The characterisation of the MSCs was determined by their cluster of differentiation (CD) marker profile. Inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied to differentiate the MSCs into ECs. Endothelial differentiation was quantitatively evaluated using flow cytometry. Real time quantitative PCR (qRT-PCR) was used to analyse mRNA expression of endothelial markers. Tube formation assay was further performed to examine the functional status of the differentiated MSCs.ResultsFlow cytometry analysis demonstrated that CD31⁺ and CD34⁺ cells increased steadily from 12% at 3 days, to 40% at 7 days, and to 60% at 14 days. Immunofluorescence staining further confirmed the expression of CD31 and CD34. qRT-PCR showed that expression of von Willebrand factor (vWF), vascular endothelial cadherin (VE-cadherin) and vascular endothelial growth factor receptor-2 (VEGFR-2) were significantly higher in the induced MSCs group compared with the uninduced MSCs group. The functional behavior of the differentiated cells was tested by tube formation assay in vitro on matrigel. Induced MSCs were capable of developing capillary networks, and progressive formation of vessel like structures was associated with increased EC population.ConclusionsThese results provide a method to efficiently promote differentiation of MSCs into ECs in vitro for potential application in the treatment of peripheral arterial disease.

http://ift.tt/2AgIuTl

Radiosensitization with an inhibitor of poly(ADP-ribose) glycohydrolase: A comparison with the PARP1/2/3 inhibitor olaparib

Publication date: January 2018
Source:DNA Repair, Volume 61
Author(s): Polly Gravells, James Neale, Emma Grant, Amit Nathubhai, Kate M. Smith, Dominic I. James, Helen E. Bryant
Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins. Inhibitors of PARPs have become an exciting and real prospect for monotherapy and as sensitizers to ionising radiation (IR). The action of PARPs are reversed by poly(ADP-ribose) glycohydrolase (PARG). Until recently studies of PARG have been limited by the lack of an inhibitor. Here, a first in class, specific, and cell permeable PARG inhibitor, PDD00017273, is shown to radiosensitize. Further, PDD00017273 is compared with the PARP1/2/3 inhibitor olaparib. Both olaparib and PDD00017273 altered the repair of IR-induced DNA damage, resulting in delayed resolution of RAD51 foci compared with control cells. However, only PARG inhibition induced a rapid increase in IR-induced activation of PRKDC (DNA-PK) and perturbed mitotic progression. This suggests that PARG has additional functions in the cell compared with inhibition of PARP1/2/3, likely via reversal of tankyrase activity and/or that inhibiting the removal of poly(ADP-ribose) (PAR) has a different consequence to inhibiting PAR addition. Overall, our data are consistent with previous genetic findings, reveal new insights into the function of PAR metabolism following IR and demonstrate for the first time the therapeutic potential of PARG inhibitors as radiosensitizing agents.

Graphical abstract

http://ift.tt/2AB7rpp

Constitutive MAP-kinase activation suppresses germline apoptosis in NTH-1 DNA glycosylase deficient C. elegans

Publication date: January 2018
Source:DNA Repair, Volume 61
Author(s): Henok Kassahun, Tanima SenGupta, Alfonso Schiavi, Silvia Maglioni, Hanne K. Skjeldam, Katarzyna Arczewska, Nicole L. Brockway, Suzanne Estes, Lars Eide, Natascia Ventura, Hilde Nilsen
Oxidation of DNA bases, an inevitable consequence of oxidative stress, requires the base excision repair (BER) pathway for repair. Caenorhabditis elegans is a well-established model to study phenotypic consequences and cellular responses to oxidative stress. To better understand how BER affects phenotypes associated with oxidative stress, we characterised the C. elegans nth-1 mutant, which lack the only DNA glycosylase dedicated to repair of oxidative DNA base damage, the NTH-1 DNA glycosylase.We show that nth-1 mutants have mitochondrial dysfunction characterised by lower mitochondrial DNA copy number, reduced mitochondrial membrane potential, and increased steady-state levels of reactive oxygen species. Consistently, nth-1 mutants express markers of chronic oxidative stress with high basal phosphorylation of MAP-kinases (MAPK) but further activation of MAPK in response to the superoxide generator paraquat is attenuated. Surprisingly, nth-1 mutants also failed to induce apoptosis in response to paraquat. The ability to induce apoptosis in response to paraquat was regained when basal MAPK activation was restored to wild type levels. In conclusion, the failure of nth-1 mutants to induce apoptosis in response to paraquat is not a direct effect of the DNA repair deficiency but an indirect consequence of the compensatory cellular stress response that includes MAPK activation.

Graphical abstract

http://ift.tt/2AC3XTp

8-oxoguanine DNA glycosylase (Ogg1) controls hepatic gluconeogenesis

Publication date: January 2018
Source:DNA Repair, Volume 61
Author(s): Katja Scheffler, Lyudmila Rachek, Panpan You, Alexander D. Rowe, Wei Wang, Anna Kuśnierczyk, Lene Kittelsen, Magnar Bjørås, Lars Eide
Mitochondrial DNA (mtDNA) resides in close proximity to metabolic reactions, and is maintained by the 8-oxoguanine DNA glycosylase (Ogg1) and other members of the base excision repair pathway. Here, we tested the hypothesis that changes in liver metabolism as under fasting/feeding conditions would be sensed by liver mtDNA, and that Ogg1 deficient mice might unravel a metabolic phenotype. Wild type (WT) and ogg1^−/− mice were either fed ad libitum or subjected to fasting for 24h, and the corresponding effects on liver gene expression, DNA damage, as well as serum values were analyzed. Ogg1 deficient mice fed ad libitum exhibited hyperglycemia, elevated insulin levels and higher liver glycogen content as well as increased accumulation of 8oxoG in mtDNA compared to age- and gender matched WT mice. Interestingly, these phenotypes were absent in ogg1^−/− mice during fasting. Gene expression and functional analyses suggest that the diabetogenic phenotype in the ogg1^−/− mice is due to a failure to suppress gluconeogensis in the fed state. The ogg1^−/− mice exhibited reduced mitochondrial electron transport chain (ETC) capacity and a combined low activity of the pyruvate dehydrogenase (PDH), alluding to inefficient channeling of glycolytic products into the citric acid cycle. Our data demonstrate a physiological role of base excision repair that goes beyond DNA maintenance, and implies that DNA repair is involved in regulating metabolism.

http://ift.tt/2ADZVtW

Application of Single Nucleotide Extension and MALDI-TOF Mass Spectrometry in Proofreading and DNA Repair Assay

Publication date: Available online 2 December 2017
Source:DNA Repair
Author(s): Kang-Yi Su, Hung-Ming Lai, Steven D. Goodman, Wei-Yao Hu, Wern-Cherng Cheng, Liang-In Lin, Ya-Chien Yang, Woei-horng Fang
Proofreading and DNA Repair are important factors in maintaining the high fidelity of genetic information during DNA replication. Herein, we designed a non-labeled and non-radio-isotopic simple method to measure proofreading. An oligonucleotide primer is annealed to a template DNA forming a mismatched site and is proofread by Klenow fragment of Escherichia coli DNA polymerase I (pol I) in the presence of all four dideoxyribonucleotide triphosphates. The proofreading excision products and re-synthesis products of single nucleotide extension are subjected to MALDI-TOF mass spectrometry (MS). The proofreading at the mismatched site is identified by the mass change of the primer. We examined proofreading of Klenow fragment with DNAs containing various base mismatches. Single mismatches at the primer terminus can be proofread efficiently. Internal single mismatches can also be proofread at different efficiencies, with the best correction for mismatches located 2-4-nucleotides from the primer terminus. For mismatches located 5-nucleotides from the primer terminus there was partial correction and extension. No significant proofreading was observed for mismatches located 6-9-nucleotides from the primer terminus. We also subjected primers containing 3′ penultimate deoxyinosine (dI) lesions, which mimic endo V nicked repair intermediates, to pol I repair assay. The results showed that T-I was a better substrate than G-I and A-I, however C-I was refractory to repair. The high resolution of MS results clearly demonstrated that all the penultimate T-I, G-I and A-I substrates had been excised last 2 dI-containing nucleotides by pol I before adding a correct ddNMP, however, pol I proofreading exonuclease tolerated the penultimate C-I mismatch allowing the primer to be extended by polymerase activity.

http://ift.tt/2AZD5PM

The global role for Cdc13 and Yku70 in preventing telomere resection across the genome

Publication date: Available online 29 November 2017
Source:DNA Repair
Author(s): James W. Westmoreland, Michael J. Mihalevic, Kara A. Bernstein, Michael A. Resnick
Yeast Cdc13 protein (related to human CTC1) maintains telomere stability by preventing 5′-3′ end resection. While Cdc13 and Yku70/Yku80 proteins appear to prevent excessive resection, their combined contribution to maintenance of telomere ends across the genome and their relative roles at specific ends of different chromosomes have not been addressable because Cdc13 and Yku70/Yku80 double mutants are sickly. Using our PFGE-shift approach where large resected molecules have slower pulse field gel electrophoresis mobilities, along with methods for maintaining viable double mutants, we address end-resection on most chromosomes as well as telomere end differences. In this global approach to looking at ends of most chromosomes, we identify chromosomes with 1-end resections and end-preferences. We also identify chromosomes with resection at both ends, previously not possible. 10-20% of chromosomes exhibit PFGE-shift when cdc13-1 cells are switched to restrictive temperature (37°C). In yku70Δ cdc13-1 mutants, there is a telomere resection "storm" with approximately half the chromosomes experiencing at least 1-end resection, ∼10kb/telomere, due to exonuclease1 and many exhibiting 2-end resection. Unlike for random internal chromosome breaks, resection of telomere ends is not coordinated. Telomere restitution at permissive temperature is rapid (<1h) in yku70Δ cdc13-1 cells. Surprisingly, survival can be high although strain background dependent. Given large amount of resected telomeres, we examined associated proteins. Up to 90% of cells have ≥1 Rfa1 (RPA) focus and 60% have multiple foci when ∼30-40 telomeres/cell are resected. The ends are dispersed in the nucleus suggesting wide distribution of resected telomeres across nuclear space. The previously reported Rad52 nuclear centers of repair for random DSBs also appear in cells with many resected telomere ends, suggesting a Rad52 commonality to the organization of single strand ends and/or limitation on interactions of single-strand ends with Rad52.

http://ift.tt/2AC3OiP

The mechanisms of K. lactis Cdc13 in telomere DNA-binding and telomerase regulation

Publication date: Available online 28 November 2017
Source:DNA Repair
Author(s): Min Hsu, Neal F. Lue
Eukaryotic chromosome ends, or telomeres, are essential for genome stability and are protected by an intricate nucleoprotein assembly. Cdc13, the major single-strand telomere-binding protein in budding yeasts, mediates critical functions in both telomere protection and telomere elongation by telomerase. In particular, the interaction between S. cerevisiae Cdc13 and telomerase subunit Est1 has long served as a paradigm for telomerase regulation. However, despite extensive investigations, the role of this interaction in regulating telomerase recruitment or activation remains controversial. In addition, budding yeast telomere repeat sequences are extraordinarily variable and how Cdc13 orthologs recognize diverse repeats is not well understood. In this report, we examined these issues using an alternative model, K. lactis. We reconstituted a direct physical interaction between purified K. lactis Cdc13 and Est1, and by analyzing point mutations, we demonstrated a close correspondence between telomere maintenance defects in vivo and Cdc13-Est1 binding defects in vitro, thus supporting a purely recruitment function for this interaction in K. lactis. Because mutations in well aligned residues of Cdc13 and Est1 in S. cerevisiae and K. lactis do not cause identical defects, our results also point to significant evolutionary divergence in the Cdc13-Est1 interface. In addition, we found that K. lactic Cdc13, unlike previously characterized orthologs, recognizes an unusually long and non-G-rich target sequence, underscoring the flexibility of the Cdc13 DNA-binding domain. Analysis of K. lactis Cdc13 and Est1 thus broadens understanding of telomere and telomerase regulation in budding yeast.

Graphical abstract

http://ift.tt/2AYO6RK

Hypersensitivity of mouse embryonic fibroblast cells defective for DNA polymerases η, ι and κ to various genotoxic compounds: Its potential for application in chemical genotoxic screening

Publication date: Available online 26 November 2017
Source:DNA Repair
Author(s): Jun-ichi Akagi, Masayuki Yokoi, Young-Man Cho, Takeshi Toyoda, Haruo Ohmori, Fumio Hanaoka, Kumiko Ogawa
Genotoxic agents cause modifications of genomic DNA, such as alkylation, oxidation, bulky adduct formation, and strand breaks, which potentially induce mutations and changes to the structure or number of genes. Majority of point mutations are generated during error-prone bypass of modified nucleotides (translesion DNA synthesis, TLS); however, when TLS fails, replication forks stalled at lesions eventually result in more lethal effects, formation of double-stranded breaks (DSBs). Here we compared sensitivities to various compounds among mouse embryonic fibroblasts derived from wild-type and knock-out mice lacking one of the three Y-family TLS DNA polymerases (Polη, Polι, and Polκ) or all of them (TKO). The compounds tested in this study include genotoxins such as methyl methanesulfonate (MMS) and nongenotoxins such as ammonium chloride. We found that TKO cells exhibited the highest sensitivities to most of the tested genotoxins, but not to the non-genotoxins. In order to quantitatively evaluate the hypersensitivity of TKO cells to different chemicals, we calculated ratios of half-maximal inhibitory concentration for WT and TKO cells. The ratios for 9 out of 10 genotoxins ranged from 2.29 to 5.73, while those for 5 nongenotoxins ranged from 0.81 to 1.63. Additionally, the two markers for DNA damage, ubiquitylated proliferating cell nuclear antigen and γ-H2AX after MMS treatment, were accumulated in TKO cells more greatly than in WT cells. Furthermore, following MMS treatment, TKO cells exhibited increased frequency of sister chromatid exchange compared with WT cells. These results indicated that the hypersensitivity of TKO cells to genotoxins resulted from replication fork stalling and subsequent DNA double-strand breaks, thus demonstrating that TKO cells should be useful for evaluating chemical genotoxicity.

Graphical abstract

http://ift.tt/2AX7r5A

DNA Replication and associated repair pathways are involved in the mutagenesis of methylated cytosine

Publication date: Available online 24 November 2017
Source:DNA Repair
Author(s): Marketa Tomkova, Michael McClellan, Skirmantas Kriaucionis, Benjamin Schuster-Böckler
Transitions of cytosine to thymine in CpG dinucleotides are the most frequent type of mutations observed in cancer. This increased mutability is commonly explained by the presence of 5-methylcytosine (5mC) and its spontaneous hydrolytic deamination into thymine. Here, we describe observations that question whether spontaneous deamination alone causes the elevated mutagenicity of 5mC. Tumours with somatic mutations in DNA mismatch-repair genes or in the proofreading domain of DNA polymerase ε (Pol ε) exhibit more 5mC to T transitions than would be expected, given the kinetics of hydrolytic deamination. This enrichment is asymmetrical around replication origins with a preference for the leading strand template, in particular in methylated cytosines flanked by guanines (GCG). Notably, GCG to GTG mutations also exhibit strand asymmetry in mismatch-repair and Pol ε wild-type tumours. Together, these findings suggest that mis-incorporation of A opposite 5mC during replication of the leading strand might be a contributing factor in the mutagenesis of methylated cytosine.

http://ift.tt/2AZD5zg

The underlying physiological basis of the desert rodent Meriones shawi's survival to prolonged water deprivation: Central vasopressin regulation on peripheral kidney water channels AQPs-2

Publication date: Available online 6 December 2017
Source:Acta Histochemica
Author(s): A. Elgot, O. El Hiba, M. Belkouch, H. Gamrani
Meriones shawi (M. shawi) is a particular semi-desert rodent known by its resistance to long periods of thirst. The aim of the present investigation is to clarify the underlying mechanisms allowing M. shawi to resist to hard conditions of dehydration. For this reason we used two different approaches: i) a morphometric study, which consists in measuring the effect of dehydration on body and kidneys weights as well as the report kidney weight/body weight, ii) By immunohistochemistry, we proceed to study the effect of dehydration on the immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2) which is a channel protein that allows water to permeate across cell membranes. Our results showed both a body mass decrease accompanied by a remarkable kidneys hypertrophy. The immunohistochemical study showed a significant increase of AQP-2 immunoreactivity in the medullar part of Meriones kidneys allowing probably to Meriones a great ability to water retention. Consistently, we demonstrate that the increased AQP-2 expression occurred together with an increase in vasopressin (AVP) expression in both hypothalamic supraoptic (SON) and paraventricular nucleus (PVN), which are a major hub in the osmotic control circuitry.These various changes seen either in body weight and kidneys or at the cellular level might be the basis of peripheral control of body water homeostasis, providing to M. shawia strong resistance against chronic dehydration.

http://ift.tt/2nAjyQt

Environmental levels of triclosan and male fertility

Abstract

Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware, although the exposure which is widespread evidence from human studies is scarce. Our study aims to investigate the relationship between triclosan exposure and male fertility. Triclosan (TCS) urinary concentrations were measured using gas chromatography coupled with tandem mass spectrometry in 315 men recruited from a male reproductive health clinic with normal sperm concentration (≥ 15 mln/ml) (WHO 2010) under 45 years of age. Participants were interviewed and provided a semen sample. TCS was detected in 84.13% of urine samples, with a median concentration of 2.83 μg/l (2.57 μg/g creatinine). A multiple linear regression analysis showed a positive association between the urinary concentrations of triclosan 50th–75th percentile and ≥ 50 percentile and percentage of sperm with abnormal morphology (p = 0.016 and p = 0.002, respectively). The study provides evidence that exposure to triclosan is associated with poorer semen quality. Future studies are needed to confirm these findings.

http://ift.tt/2jmMcjJ

Characteristics of different molecular weight EPS fractions from mixed culture dominated by AnAOB and their role in binding metal ions

Abstract

Ultraviolet-visible (UV-Vis) absorbance spectra were adopted to quantify the binding of metal ions (e.g., Fe(III), Cu(II), Pb(II), and Cd(II)) on three MW fractions (> 100, 10~100, and < 10 k Da) of extracellular polymeric substances (EPS) extracted from mixed cultures dominated by anaerobic ammonium-oxidizing bacteria (AnAOB). The results showed that the AnAOB EPS with different MW size ranges all had strongest binding capability of Fe(III), and the lowest binding capability of Cd(II). The complexation ability of metal ions for the EPS of AnAOB with molecular weight < 10 kDa was stronger than EPS with >100 and 10~100 kDa, very likely because of the contribution of the tyrosine-, tryptophan-, and aromatic protein-like components. It was obvious that the different size fractions of EPS affect the metal binding ability. Essentially, the content of proteins, polysaccharides, TOC, and UVA₂₅₄ distributed within various MW fractions of EPS from AnAOB were different, as well as the different fluorescent components and total functional groups.

http://ift.tt/2BFWTV3

Amicarbazone degradation promoted by ZVI-activated persulfate: study of relevant variables for practical application

Abstract

Alarming amounts of organic pollutants are being detected in waterbodies due to their ineffective removal by conventional treatment techniques, which warn of the urgent need of developing new technologies for their remediation. In this context, advanced oxidation processes (AOPs), especially those based on Fenton reactions, have proved to be suitable alternatives, due to their efficacy of removing persistent organic compounds. However, the use of ferrous iron in these processes has several operational constraints; to avoid this, an alternative iron source was here investigated: zero-valent-iron (ZVI). A Fenton-like process based on the activation of a recently explored oxidant-persulfate (PS)—with ZVI was applied to degrade an emerging contaminant: Amicarbazone (AMZ). The influence of ZVI size and source, PS/ZVI ratio, pH, UVA radiation, dissolved O₂, and inorganic ions was evaluated in terms of AMZ removal efficiency. So far, this is the first time these parameters are simultaneously investigated, in the same study, to evaluate a ZVI-activated PS process. The radical mechanism was also explored and two radical scavengers were used to determine the identity of major active species taking part in the degradation of AMZ. The degradation efficiency was found to be strongly affected by the ZVI dosage, while positively affected by the PS concentration. The PS/ZVI system enabled AMZ degradation in a wide range of pH, although with a lower efficiency under slightly alkaline conditions. Dissolved O₂ revealed to play an important role in reaction kinetics as well as the presence of inorganic ions. UVA radiation seems to improve the degradation kinetics only in the presence of extra O₂ content. Radicals quenching experiments indicated that both sulfate (SO₄^•−) and hydroxyl (^•OH) radicals contributed to the overall oxidation performance, but SO₄^•− was the dominant oxidative species.

http://ift.tt/2jnVLij

Reply

Publication date: Available online 6 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Fernando Sergio Leitao Filho, Seung Won Ra, Andre Mattman, Robert S. Schellenberg, Don D. Sin

http://ift.tt/2B0gpio

Chronic obstructive pulmonary disease exacerbation frequency and serum IgG levels

Publication date: Available online 6 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Juthaporn Cowan, Sunita Mulpuru, Gonzalo Alvarez, Vicente Corrales-Medina, Donald W. Cameron

http://ift.tt/2AB3wcb

Cutometric assessment of elasticity of skin with striae distensae following carboxytherapy

Summary

Objective

The aim of the study was to evaluate the effectiveness of carboxytherapy in the treatment of striae distensae. Additionally, discomfort and side effects associated with the treatment were assessed.

Materials and methods

This study involved 15 women aged 22-40 years. They underwent 3 sessions of carboxytherapy at one-week intervals. Treatment was performed in skin area within stretch marks located on stomach, buttocks, and thighs. Cutometric probe was used to evaluate skin elasticity. Four measurements were performed—immediately before each treatment and one month after the last session. Photographic documentation was made before and after a series of treatment to perform clinical evaluation of changes in skin condition.

Results

Statistical analysis of results obtained with the use of Cutometer (R2 and R8 parameters) demonstrated that carboxytherapy significantly improved skin elasticity within stretch marks (P < .05). The analysis of photographic documentation revealed 58% improvement in stretch mark visibility. The width and length of stretch marks decreased, and their color became more like the natural color of the skin. Carboxytherapy is associated with moderate pain/discomfort. The occurrence of hematoma is the main side effect of this procedure.

Conclusions

Carboxytherapy seems to be an effective method of reducing stretch marks. This procedure is safe, and it can be performed without the risk of complications. Moreover, it does not require special postoperative convalescence. Photographic documentation is a method of assessment of aesthetic procedures effectiveness, which is complementary to other objective methods (eg, the use of MPA probes).

http://ift.tt/2k23jGY

Improved stratification of pT1 melanoma according to the 8th American Joint Committee on Cancer staging edition criteria: A Dutch population-based study

Publication date: Available online 5 December 2017
Source:European Journal of Cancer
Author(s): D. Verver, W.J. Louwman, S. Koljenović, C. Verhoef, D.J. Grünhagen, A.C.J. van Akkooi
IntroductionThe 8th American Joint Committee on Cancer (AJCC) staging edition includes revisions regarding pT1 melanomas. We aimed to evaluate the expected impact of this edition on staging and survival in the Dutch pT1 melanoma population.MethodsIn total, 32,935 pT1 melanoma patients, whose data were retrieved from the Netherlands Cancer Registry between 2003 and 2015, were included in the study. Patients were stratified by the 6th AJCC edition (cohort 1: 2003–2009) and 7th edition (cohort 2: 2010–2015) and all reclassified according to the 8th edition. Stage migration, sentinel lymph node biopsy (SLNB) positivity rates and relative survival were analysed. Agreement between staging systems was calculated by Cohen's kappa coefficient.ResultsIn cohort 2, restaging according to the 8th edition led to an increase of 7% in the total number of patients staged pT1b. The kappa score for agreement between the 6th and 8th edition was 0.15 and 0.25 for agreement between 7th and 8th edition. Restaging according to the 8th edition resulted in a higher SLNB positivity rate for pT1b patients than pT1a patients (8% versus 5%, p = 0.08). Relative survival curves were predominantly similar between the staging editions.ConclusionsImplementation of the 8th AJCC staging edition will presumably not have major impact on the total number of Dutch pT1b patients. Consequently, the number of patients eligible for SLNB would roughly remain similar. In terms of SLNB positivity, the selection of high-risk pT1 melanoma patients is likely to improve. In addition, the 8th edition criteria for pT1 melanoma seem more workable for pathologists.

http://ift.tt/2AXC3E0

HER2 copy number of circulating tumour DNA functions as a biomarker to predict and monitor trastuzumab efficacy in advanced gastric cancer

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): Haixing Wang, Beifang Li, Zhentao Liu, Jifang Gong, Lin Shao, Jun Ren, Yunyun Niu, Shiping Bo, Zhongwu Li, Yumei Lai, Sijia Lu, Jing Gao, Lin Shen
BackgroundHER2 status is significant to trastuzumab therapy; however, it is difficult to determine HER2 status accurately with few pieces of biopsies from advanced gastric cancer (AGC) due to highly heterogeneity and invasive behaviour, which will be investigated in this study.MethodsFifty-six patients with AGC were included in this study. Primary tumour tissues and matched plasmas before medication from 36 patients were retrospectively collected, and the other 20 patients with primary tumour tissues and paired plasmas were prospectively collected. HER2 expression and amplification in 56 tumour tissues were determined by immunohistochemistry (IHC) and dual in situ hybridisation (DISH), and HER2 copy number in 135 circulating tumour DNAs (ctDNAs) was judged by next-generation sequencing.ResultsFor tumour tissues, HER2 amplification by DISH was most commonly found in patients with HER2 score 3+by IHC. For plasmas, HER2 amplification defined as HER2 copy number >2.22 was identified in 26 of 56 patients. There was a high concordance of HER2 amplification between ctDNA and tumour tissues, suggesting that ctDNA could function as an alternative to screen HER2-targeted population. Moreover, the changes of HER2 copy number in ctDNA could efficiently monitor trastuzumab efficacy, the power of which was superior to commonly used markers carcinoembryonic antigen (CEA) and CA199, suggesting its potential role in clinical practice.ConclusionctDNA for HER2 analysis was strongly recommended to serve as a surrogate to screen trastuzumab-suitable population and monitor trastuzumab efficacy.

http://ift.tt/2AWX0z0

The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): Magdalena Lycken, Linda Drevin, Hans Garmo, Pär Stattin, Jan Adolfsson, Ingela Franck Lissbrant, Lars Holmberg, Anna Bill-Axelson
BackgroundSymptoms of terminal cancer have previously been reported as undertreated. The aim of this study was to assess the use of palliative medications before death from prostate cancer.MethodsThis Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer.ResultsWe included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47–0.66 for >85 years versus <70 years) and (OR 0.78, 95% CI: 0.66–0.92 for unmarried without children versus married with children).ConclusionOur results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer.

http://ift.tt/2AC2VXI

C-statistic: A brief explanation of its construction, interpretation and limitations

Publication date: Available online 5 December 2017
Source:European Journal of Cancer
Author(s): S.J. Caetano, G. Sonpavde, G.R. Pond

http://ift.tt/2AWWS2u

Toxocara species exposure, symptoms of asthma, and fractional exhaled nitric oxide in the US population

Asthma is a major cause of morbidity in the United States.1 Toxocariasis is caused by exposure to the eggs of the nematodes Toxocara canis and Toxocara cati.2,3 Clinic-based studies have reported the association of Toxocara species with asthma. A study using data from the Third National Health and Nutrition Examination Survey (NHANES III) of 1988 to 1994 examined the association between Toxocara species infection and lung function in the United States.4 Infection was negatively associated with forced expiratory volume in 1 second.

http://ift.tt/2AAT1HY

Spectrum and prevalence of reactions to marijuana in a Colorado allergy practice

Since the legalization of medical marijuana (MJ) and recreational MJ in certain states, an increasing number of patients with allergy are presenting from MJ exposure. Most have substantial exposure from industrial cultivation or are heavy consumers, indicating that cannabis is a mild allergen.

http://ift.tt/2ktVJZA

Could calcium channel blockers treat 2 illnesses with 1 pill?

Ever since Middleton's1 suggestion that excessive permeability of airway cells to calcium ions might play a role in the underlying mechanism of bronchial hyperresponsiveness (BHR) and asthma, researchers have questioned whether calcium channel blockers (CCBs) might be efficacious in the treatment of this illness. Their potential utility makes a great deal of sense, because cytoplasmic calcium is involved in bronchoconstriction, mast cell mediator release, vagal reflex stimulation, airway mucous gland secretion, chemotaxis of eosinophils, and possibly even smooth muscle remodeling.

http://ift.tt/2iYrBFn

http://ift.tt/2kteGf0

Editorial Board

http://ift.tt/2j1L9bP

Innate lymphoid cells and allergic disease

Allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis, are substantial causes of morbidity and mortality in developing and developed countries. An expansive set of cellular mediators and mechanisms have been identified that contribute to the initiation or exacerbation of allergic disease. During the past decade, the discovery of a new subset of leukocytes known as innate lymphoid cells (ILCs) has great expanded our understanding of the pathogenesis of allergic disease.

http://ift.tt/2ksyDmg

Instructions for Authors

http://ift.tt/2j157U4

Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO

The Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) study was designed to better understand the types of patients who are begun on omalizumab in the real-world setting, including asthma burden, comorbidities, and biomarker profiles, and to evaluate what clinical parameters might be associated with better outcomes with the use of this biologic agent. In this month's issue of the Annals, Griffin et al1 report on the first of these 2 outcomes.

http://ift.tt/2krEw2R

Burden of skin pain in atopic dermatitis

Atopic dermatitis (AD) is associated with itch, skin inflammation and barrier disruption, and scratching, all of which may be associated with skin pain.

http://ift.tt/2j1KV4t

Author Index to Volume 119, 2017

Abraham T, [Letters] 558

http://ift.tt/2j1KSWl

Information for Readers

http://ift.tt/2kuTViR

Increasing our knowledge base of asthma

During the past decade, there has been an explosion in our knowledge of asthma. There are new descriptions of phenotypes, endotypes, and even genotypes. New approaches to management have been and continue to be developed. The realization and characterization of a spectrum of overlap with chronic obstructive pulmonary disease (COPD) in many patients with asthma have been reported in detail and approaches to management of patients with severe asthma continue on the forefront. These and other aspects of asthma are well represented in the more than 200 articles published on asthma since 2015 in the Annals of Allergy, Asthma and Immunology.

http://ift.tt/2j1Lew9

The clinical role of fractional exhaled nitric oxide in asthma control

The potential role and characteristics of fractional exhaled nitric oxide (FeNO) remain unclear in the treatment of asthma.

http://ift.tt/2kuUUzO

Contents: Volume 45

http://ift.tt/2BQT4NG

Keyword index: Volume 45

http://ift.tt/2k3Rccr

Announcements

Dear Colleagues,

http://ift.tt/2BPWAbi

EACMFS Awards

The Council of EACMFS wishes to ensure that all members of the Association are aware of the current awards and prizes that are available. These are designed to provide educational support and also to allow the opportunity for trainees and those who have recently achieved specialist status to visit units outside their own departments.

http://ift.tt/2k30dCu

Author Index: Volume 45

http://ift.tt/2BPnhgd

Editorial Board

http://ift.tt/2k0EzyS

Cutometric assessment of elasticity of skin with striae distensae following carboxytherapy

Summary

Objective

The aim of the study was to evaluate the effectiveness of carboxytherapy in the treatment of striae distensae. Additionally, discomfort and side effects associated with the treatment were assessed.

Materials and methods

Results

Conclusions

http://ift.tt/2k23jGY

Toxocara species exposure, symptoms of asthma, and fractional exhaled nitric oxide in the US population

Spectrum and prevalence of reactions to marijuana in a Colorado allergy practice

Could calcium channel blockers treat 2 illnesses with 1 pill?

http://ift.tt/2kteGf0

Editorial Board

http://ift.tt/2j1L9bP

Innate lymphoid cells and allergic disease

Instructions for Authors

http://ift.tt/2j157U4

Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO

Burden of skin pain in atopic dermatitis

Atopic dermatitis (AD) is associated with itch, skin inflammation and barrier disruption, and scratching, all of which may be associated with skin pain.

http://ift.tt/2j1KV4t

Author Index to Volume 119, 2017

Abraham T, [Letters] 558

http://ift.tt/2j1KSWl

Information for Readers

http://ift.tt/2kuTViR

Increasing our knowledge base of asthma

The clinical role of fractional exhaled nitric oxide in asthma control

The potential role and characteristics of fractional exhaled nitric oxide (FeNO) remain unclear in the treatment of asthma.

http://ift.tt/2kuUUzO

Flat foveal contour simulating macular hole

Description

A 40-year-old healthy female was referred for macular hole in his both eyes detected during routine examination. Visual acuity was 20/20 OU unaided. Ocular examination of OD was unremarkable except for the presence of round red lesion at fovea (figure 1A, arrow) that was more prominent on green reflectance imaging (figure 1B, arrow). Spectral-domain optical coherence tomography showed a flattened foveal contour (figure 1C, arrows), which explained the appearance of macular hole. Similar findings were seen in OS. There were no ocular or systemic features suggestive of albinism.

Figure 1

Multicolour scanning laser image of right eye showing small red lesion (arrow) simulating macular hole (A) that is better seen on red free image (B). Apparent macular hole corresponds to flat foveal contour on optical coherence tomography (C).

The foveal contour and anatomy may vary...

http://ift.tt/2AfLlM7

Complication of deep brain stimulation for Parkinsons disease

Description

A 58-year-old man with advanced Parkinson disease diagnosed 13 years before, was admitted for surgical placing of continuous bilateral high-frequency stimulation of the subthalamic nucleus.

The procedure was uneventful (lead used Medtronic DBS 3387; antibiotic prophylaxis: cefazolin 2 g at time of anaesthetic induction and 1 g every 8 hours in the first 24 hours) with a postoperative control CT scan showing good placement of the electrodes and no abnormalities (figure 1). The stimulation was switched on 72 hours after the procedure and within 24 hours the patient presented two epileptic seizures controlled with diazepam and stimulation was switched off. The head CT showed intra-axial hypodensity more prominent in the frontal area with a gaseous collection and oedema surrounding the right electrode pathway (figure 2). At the time there was no fever, no increase in inflammatory markers and a normal cell count in the lumbar puncture. However, antibiotic therapy (ceftriaxone...

http://ift.tt/2B8bPiP

Mycobacterium tuberculosis of the elbow joint

Mycobacterium tuberculosis(TB) affecting the elbow joint is rarely reported in the developed world. We present the case of an 85-year-old Caucasian female who complained of a chronically discharging and painful wound across her left elbow during her admission for an ischaemic stroke. This was initially deemed to be either a bursitis or local manifestation of amyloid by her general practitioner and dermatologist respectively prior to admission. She was commenced on flucloxacillin by the medical team for presumed cellulitis with minimal response. A synovial fluid sample and repeated wound swabs yielded no growth from routine bacterial culture. Radiological assessment together with knowledge of her husband having previous TB raised the possibility of TB arthritis. Synovial fluid aspirate was subsequently sent for acid–alcohol fast bacilli microscopy and mycobacterial culture that confirmed M. tuberculosis. She was consequently started on multidrug TB therapy, over a year after the onset of her symptoms.

http://ift.tt/2Afmloa

Lipoid proteinosis: towards predictive clinical clues

http://ift.tt/2k2OPqg

Lipoid proteinosis: towards predictive clinical clues

http://ift.tt/2k2OPqg

Predictors of Response and Survival in Locally Advanced Adenocarcinoma of the Pancreas Following Neoadjuvant GTX with or Without Radiation Therapy

AbstractLessons Learned. There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer.Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement.Background.In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (≥2 mm margins), and survival.Methods.All patients had baseline magnetic resonance imaging (MRI) and/or computed tomography (CT) scans and endoscopic ultrasound. A baseline positron emission tomography‐computed tomography (PET‐CT) was performed in 39 patients. The scans were reviewed by two radiologists.GTX (gemcitabine 750 mg/m2 and docetaxel 30 mg/m2 on days 4 and 11 with capecitabine 1,500 mg/m2 days 1–14) was administered on a 3‐week schedule for 6 cycles to patients with both arterial and venous‐only involvement. Patients in the arterial arm received GX/RT before surgery, and those in the venous arm received GX/RT after R1 resection. Standard‐dose RT was delivered by intensity‐modulated radiation therapy (IMRT) or conformal fields to 5040 cGy along with capecitabine for 5 days and gemcitabine on day 5 of weeks 1, 2, 4, and 5 of RT, starting with the first full week of RT.A cancer antigen test 19‐9 (CA 19‐9) was obtained at baseline and days 4 and 11 of each cycle. The rate of change in CA 19‐9 was calculated using the formula: (Log10 CA 19‐9 time 0) − (Log10 CA 19‐9 at 9 weeks)/9 weeks. This was derived based on the observation that the fall in CA 19‐9 following effective chemotherapy is a second‐order function.Results.Of the 34 patients with arterial involvement and 11 with extensive venous involvement who met the eligibility criteria and began GTX, only 5 patients in the arterial arm did not undergo subsequent resection. The remaining 40 patients were included in this analysis of presenting parameters with respect to R0 resection, disease‐free survival (DFS), and overall survival (OS). R0 resection was achieved in 28 of 40 patients (70%), and R1 resection in the remaining 12 (30%). The OS after R0 resection was a median 37 months (95% confidence interval [CI]: 29.3–44.7) compared with 29 months (95% CI: 28.5–41.5) for those with R1 resection.Excluding four postoperative deaths, median DFS for the 25 (71%) with R0 resection was 31 months (95% CI: 11.3–51.1), and the median DFS for R1 resection was only 14 months (95% CI: 11.1–17). Eleven of the twenty‐eight (39%) patients achieving R0 resection have not relapsed (median = 45 months, range = 25–71 months).Conclusion.R0 resection, the goal of neoadjuvant treatment, can be achieved in 70% of patients presenting with locally advanced pancreatic cancer. The median DFS was 31 months (95% CI: 11. 3–51.1). No relationship was found with tumor size, degree of vascular involvement, carcinoembryonic antigen test (CEA), CA 19‐9, degree of tumor regression on scan, fall in CA 19‐9, or SUV on PET scan and subsequent survival.

http://ift.tt/2AgmtUH

Decision‐Making Capacity for Chemotherapy and Associated Factors in Newly Diagnosed Patients with Lung Cancer

AbstractBackground.The objective of this study was to assess decision‐making capacity in patients newly diagnosed with lung cancer, clinical factors associated with impaired capacity, and physicians' perceptions of patients' decision‐making capacity.Materials and Methods.We recruited 122 patients newly diagnosed with lung cancer. One hundred fourteen completed the assessment. All patients were receiving a combination of treatments (e.g., chemotherapy, chemo‐radiotherapy, or targeted therapy). Decision‐making capacity was assessed using the MacArthur Competence Tool for Treatment. Cognitive impairment, depressive symptoms, and frailty were also evaluated. Physicians' perceptions were compared with the ascertainments.Results.Twenty‐seven (24%, 95% confidence interval [CI], 16–31) patients were judged to have incapacity. Clinical teams had difficulty in judging six (22.2%) patients for incapacity. Logistic regression identified frailty (odds ratio, 3.51; 95% CI, 1.13–10.8) and cognitive impairment (odds ratio, 5.45; 95% CI, 1.26–23.6) as the factors associated with decision‐making incapacity. Brain metastasis, emphysema, and depression were not associated with decision‐making incapacity.Conclusion.A substantial proportion of patients diagnosed with lung cancer show impairments in their capacity to make a medical decision. Assessment of cognitive impairment and frailty may provide appropriate decision‐making frameworks to act in the best interest of patients.Implications for Practice.Decision‐making capacity is the cornerstone of clinical practice. A substantial proportion of patients with cancer show impairments in their capacity to make a medical decision. Assessment of cognitive impairment and frailty may provide appropriate decision‐making frameworks to act in the best interest of patients.

http://ift.tt/2B8BwzQ

Successful Ovarian Stimulation for Fertility Preservation in a Patient with Chronic Myeloid Leukemia: Switch from Nilotinib to Interferon‐α

AbstractThe development of tyrosine‐kinase inhibitors (TKIs) has improved survival of patients with chronic myeloid leukemia (CML). Some patients may become resistant to TKIs and require hematopoietic stem cell transplant (HSCT) that is highly gonadotoxic. Fertility preservation with ovarian stimulation might be indicated but is challenging if patients need to remain on TKIs until HSCT because TKIs may compromise follicular development and response to ovarian stimulation. We report the case of a patient with CML resistant to TKI and planned for an HSCT, in which treatment by TKI was replaced by interferon‐α before and during ovarian stimulation for fertility preservation. Successful ovarian stimulation was performed, allowing cryopreservation of nine zygotes. Hematopoietic stem cell transplantation was performed, and at present, 3 years later, the patient presents a sustained major molecular response.

http://ift.tt/2AgmhEX

The Role of Rituximab in Chronic Lymphocytic Leukemia Treatment and the Potential Utility of Biosimilars

AbstractChronic lymphocytic leukemia (CLL) is managed with observation for asymptomatic or clinically silent disease; pharmacologic intervention is generally required for symptomatic patients with clinically significant adenopathy or cytopenia. In the front‐line treatment of CLL, the current standard‐of‐care includes chemotherapy in combination with an anti‐CD20 monoclonal antibody (e.g., rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the evolving treatment paradigm toward targeted therapy, it is likely that rituximab (plus chemotherapy), with or without targeted agents, will retain a significant role in CLL treatment. However, patents for many biologics, including rituximab, have expired or will expire in the near future. Furthermore, access to rituximab has remained challenging, particularly in countries with restricted resources. Together, these concerns have prompted the development of safe and effective rituximab biosimilars. The term "biosimilar" refers to a biologic that is highly similar to an approved reference (originator) product, notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences in purity, potency, or safety. Biosimilars are developed to treat the same condition(s) using the same treatment regimens as an approved reference biologic and have the potential to increase access to more affordable treatments. We review the importance of rituximab in the current treatment of CLL, the scientific basis of its future role in combination with chemotherapy, and the role of new and emerging agents in the treatment of CLL, which could potentially be used in combination with rituximab biosimilars. We also discuss rituximab biosimilars currently in development.Implications for Practice.Front‐line treatments for chronic lymphocytic leukemia (CLL) include chemotherapy in combination with an anti‐CD20 monoclonal antibody (e.g., rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the evolving treatment paradigm, it is likely rituximab (plus chemotherapy) and targeted agents undergoing clinical evaluation will retain a significant role in CLL treatment. However, patents for many biologics, including rituximab, have expired or will expire in the near future and, in many regions, access to rituximab remains challenging. Together, these concerns have prompted the development of safe and effective rituximab biosimilars, with the potential to increase access to more affordable treatments.

http://ift.tt/2B9b74J

Clinical Activity of Pazopanib in Patients with Advanced Desmoplastic Small Round Cell Tumor

AbstractBackground.Desmoplastic small round cell tumor (DSRCT) is an aggressive, often fatal soft tissue sarcoma that lacks an optimal salvage regimen. We retrospectively reviewed data from 29 pretreated DSRCT patients who received pazopanib at MD Anderson Cancer Center after failure of standard chemotherapies.Subjects, Materials, and Methods.Medical records of patients treated from January 2012 to December 2016 were reviewed and regression analyses were performed. Median progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan‐Meier method and differences in survival were assessed by a log‐rank test. A landmark statistical analysis was used to assess OS at a predefined 12‐week time point following pazopanib initiation.Results.The mean age at pazopanib treatment was 27.5 years (range, 6.3–50.1 years). According to RECIST 1.1 criteria, 16 patients (55%) had stable disease, 1 patient (3%) had partial response, 1 patient (3%) had complete response, and 11 patients (38%) had progressive disease. Estimated median PFS was 5.63 months (95% confidence interval [CI]: 3.23–7.47). Median OS was 15.7 months (95% CI: 10.3–32.4). As of December 2016, 11 patients (38%) were still alive, with a median follow‐up time of 16.8 (range 3.8–30.1) months. Doses between 400 and 800 mg were included. Pazopanib was well tolerated and 23 (79%) of the patients continued it until progression or death, 4 discontinued because of side effects, and 2 were still on pazopanib at the time of data analysis.Conclusion.In the largest study conducted to date in DSRCT, pazopanib was well tolerated and clinically active in heavily pretreated patients who otherwise lack good treatment options.Implications for Practice.Desmoplastic small round cell tumor (DSRCT) is a rare, extremely aggressive soft tissue sarcoma subtype that most commonly occurs in adolescent and young adult males. No DSRCT‐specific therapies exist, and for lack of a better treatment approach, current therapies have relied upon U.S. Food and Drug Administration‐approved drugs like pazopanib that exhibit clinical activity in other sarcoma subtypes. Herein, we describe the largest experience to date using pazopanib as salvage treatment in heavily pretreated DSRCT patients. Pazopanib was well tolerated and clinically active, surpassing predefined metrics proposed by the European Organization for Research and Treatment of Cancer indicative of "active" sarcoma drugs (5.63 months progression‐free survival [PSF], with 62% of the study population achieving progression‐free survival at 12 weeks).

http://ift.tt/2Agi6IY

Diagnostic and treatment effects of sialendoscopy for patients with swelling of the parotid gland when sialoliths are undetected with computed tomography

Publication date: Available online 6 December 2017
Source:Auris Nasus Larynx
Author(s): Norio Kondo, Toshio Yoshihara, Yukie Yamamura, Kaoru Kusama, Eri Sakitani, Yukako Seo, Mayako Tachikawa, Keiko Kujirai, Erika Ono, Yasuyo Maeda, Tomohito Nojima, Akiko Tamiya, Emiri Sato, Manabu Nonaka
Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct. Balloon expansion of the duct was performed in these 2 patients and a steroid drug was injected into the duct in one patient. Complete remission was archived in one patient treated with sialendoscopy. Three patients had sialolithiasis. Microsialoliths and/or white floating matter was observed and removed using sialendoscopy. All patients experienced complete remission. In cases of Sjögren syndrome and recurrent parotitis, sialendoscopic surgery was performed, but the symptoms showed no improvement. For patients with microsialoliths, sialendoscopy may be most useful for diagnosis and treatment when the sialoliths are not detected with CT imaging. At present, sialendoscopic surgery have limitation in the treatment of Stensen's duct stenosis and may similarly have limitation in the treatment of Sjögren's syndrome and recurrent parotitis.

http://ift.tt/2j0qFR3

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τετάρτη 6 Δεκεμβρίου 2017

Graphical abstract

Graphical abstract

Graphical abstract

Graphical abstract

Graphical abstract

Graphical abstract

Graphical abstract

Graphical abstract

Abstract

Abstract

Abstract

Summary

Objective

Materials and methods

Results

Conclusions

Summary

Objective

Materials and methods

Results

Conclusions

Αρχειοθήκη ιστολογίου